The long-term goal of the present project is to understand the cortical control of voluntary movements used to reach out, grasp and manipulate. These movements typically are considered as distinct processes, controlled from proximal versus distal sub-regions of the upper extremity representation in the primary motor cortex, and influenced via distinct inputs from dorsal versus ventral areas of the premotor cortex, respectively. Here we propose to investigate the neurophysiological activity underlying the seamless integration of reaching, grasping, and manipulation into a single coordinated motor act. Specifically, the present proposal aims to: 1) determine whether single neurons and other neurophysiological activity in the primary motor cortex, dorsal premotor cortex and ventral premotor cortex are modulated in relation to reaching, to grasping, or to both; 2) determine how and where manipulative actions of the arm and hand are represented in the primary motor and premotor cortex; and 3) to determine how the grip forces and the load forces used in manipulation are represented and controlled. Improved understanding of these processes will lead to improved rehabilitation for functional recovery and to improved neuro-prosthetic devices for patients affected by numerous neurological diseases including stroke, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain or spinal cord injury, and cerebral palsy. PUBLIC HEALTH RELEVANCE: The long-term goal of the present project is to understand how the brain controls movements of the arm and hand used to reach out, grasp and manipulate objects. The present experiments will examine how neurophysiological activity in motor areas of the cerebral cortex integrates the seamless control of the multiple stages of reaching, grasping and manipulation. Improved understanding of these processes will lead to improved rehabilitation to functional recovery and improved neuro-prosthetic devices for patients affected by numerous neurological diseases including stroke, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain or spinal cord injury, and cerebral palsy.